Trastuzumab in Treating Patients With Locally Advanced or Metastatic Synovial Sarcoma

OBJECTIVES:

Primary

• Determine the response rate (confirmed complete response and partial response) in patients with HER2/neu-overexpressing locally advanced or metastatic synovial sarcoma treated with trastuzumab (Herceptin^®).

Secondary

• Determine the frequency and severity of toxic effects of this drug in these patients.
• Determine overall survival and progression-free survival of patients treated with this drug.
• Correlate, preliminarily, SYT-SSX translocation, HER2/neu expression, and monophasic and biphasic phenotype with clinical outcomes in patients treated with this drug.

OUTLINE: This is a pilot, multicenter study.

Patients receive trastuzumab (Herceptin^®) IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 weeks until disease progression and then every 6 months for up to 2 years from study entry.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 10-40 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed synovial sarcoma meeting 1 of the following stage criteria:

• Locally advanced disease, defined as 1 of the following:

• Incurable by conventional multidisciplinary therapy, including surgery
• Surgically resectable only with significant morbidity
• Metastatic disease
• Tumor HER2/neu positive (2+ or 3+) by immunohistochemistry
• Tumor tissue must be available AND patient must be willing to allow specimen submission
• Measurable disease
• No known CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3
• Hemoglobin > 8 g/dL
• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)
• SGOT and/or SGPT < 1.5 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine < 1.5 times ULN OR
• Creatinine clearance > 60 mL/min

Cardiovascular

• LVEF > 45% by MUGA

Gastrointestinal

• No active peptic ulcer disease
• No active gastrointestinal bleeding
• No active inflammatory bowel disease

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No known HIV positivity
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent filgrastim (G-CSF)

Chemotherapy

• At least 3 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 60 days since prior radiotherapy to the target lesion*
• No concurrent radiotherapy NOTE: *Lesion must have demonstrated disease progression after completion of therapy

Surgery

• At least 21 days since prior major surgery and recovered

Other

• At least 60 days since prior embolization or radiofrequency ablation to the target lesion* NOTE: *Lesion must have demonstrated disease progression after completion of therapy